cholesterol side-chain cleavage gene expression in theca cells augmented transcriptional regulation and mrna stability in polycystic ovary syndrome胆固醇侧链乳沟鞘细胞中基因表达增强多囊卵巢综合征的mrna转录调控和稳定.pdfVIP

Cholesterol Side-Chain Cleavage Gene Expression in Theca Cells: Augmented Transcriptional Regulation and mRNA Stability in Polycystic Ovary Syndrome 1. 1. 1 2 Jessica K. Wickenheisser , Jessica M. Biegler , Velen L. Nelson-DeGrave , Richard S. Legro , Jerome F. Strauss III3, Jan M. McAllister1,2* 1 Department of Pathology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America, 2 Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America, 3 Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America Abstract Hyperandrogenism is characteristic of women with polycystic ovary syndrome (PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long-term culture produce elevated levels of progestins and androgens compared to normal theca cells. Augmented steroid production in PCOS theca cells is associated with changes in the expression of genes for several steroidogenic enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain cleavage. Here, we further examined CYP11A1 gene expression, at both the transcriptional and post-transcriptional level in normal and PCOS theca cells propagated in long-term culture utilizing quantitative RT-PCR, functional promoter analyses, and mRNA degradation studies. The minimal element(s) that conferred increased basal and cAMP-dependent CYP11A1 promoter function were determined. CYP11A1 mRNA half-life in normal and PCOS theca cells was compared. Results of these cumulative studies showed that basal a